Julia Gunkel

Neuro-Imaging Findings in Infants with Congenital Cytomegalovirus Infection: Relation to Trimester of Infection

Background: Congenital cytomegalovirus (cCMV) infection early in pregnancy may result in major disabilities. Cerebral abnormalities detected using cranial ultrasound (cUS) and magnetic resonance imaging (MRI) have been related to neurological sequelae. Objective: To evaluate the additional value of MRI and assess the relationship between time of infection during pregnancy and outcome in infants with cCMV infection. Methods and Study Design: Demographic and clinical data were collected in infants with cCMV infection (1992-2013). Trimester of infection, neuro-imaging results and outcome were reviewed. Cerebral abnormalities were categorized into none, mild (lenticulostriate vasculopathy, germinolytic cysts, high signal intensity on T2-weighted images) and severe (migrational disorder, ventriculomegaly, cerebellar hypoplasia). Results were statistically analysed. Results: Thirty-six infants were eligible for analysis. cUS was performed in all and cranial MRI in 20 infants. Migrational disorders were only diagnosed using MRI (p < 0.01). In 17 infants trimester of infection was ascertained. Seven out of 10 infants infected during the first trimester had severe abnormalities on cUS (5 confirmed on MRI) and adverse sequelae; 3 had no/mild abnormalities on cUS/MRI and normal outcome. Two out of 3 infants infected during the second trimester with no/mild abnormalities on cUS/MRI had normal outcome; 1 with mild cUS and MRI abnormalities developed sensorineural hearing loss. Four infants infected during the third trimester with no/mild abnormalities on cUS/MRI had normal outcome. Conclusion: Infants with a first trimester cCMV infection are most at risk of severe cerebral abnormalities and neurological sequelae. MRI, and not cUS, enables an early diagnosis of migrational disorders, which can improve prediction of outcome.

Urine is superior to saliva when screening for postnatal CMV infections in preterm infants

BACKGROUND Cytomegalovirus (CMV) is the most frequently contracted virus in preterm infants. Postnatal infection is mostly asymptomatic but is sometimes associated with severe disease. To diagnose an infection, urine or saliva samples can be tested for CMV-DNA by real-time polymerase chain reaction (rtPCR). Although the diagnostic accuracy of testing saliva samples has not been determined in preterm infants, saliva is widely used because it is easier to obtain than urine. OBJECTIVES To determine whether screening of saliva is equivalent to urine to detect a postnatal CMV infection in preterm infants. STUDY DESIGN Between 2010 and 2013 saliva and urine samples were collected from infants admitted to the Neonatal Intensive Care Unit of the University Medical Center Utrecht and born with a gestational age (GA) below 32 weeks. Urine samples were obtained within three weeks after birth and urine and saliva samples at term equivalent age (40 weeks GA) and tested for CMV-DNA by rtPCR. Infants with a congenital CMV infection were excluded. RESULTS Of 261 preterm infants included in the study, CMV-DNA was detected in urine of 47 and in saliva of 43 children. Of 47 infants with postnatal CMV infection, CMV was detected in 42 saliva samples (sensitivity 89.4%; CI 76.9-96.5). Of 214 children without postnatal CMV infection, one saliva sample tested positive for CMV (specificity 99.5%; CI 97.4-99.9). CONCLUSIONS Screening saliva for CMV-DNA by rtPCR is inferior to urine to diagnose postnatal CMV infections in preterm infants.

Outcome of Preterm Infants With Postnatal Cytomegalovirus Infection

In this prospective study, we investigate neurodevelopmental outcomes, including hearing, of a large cohort of preterm infants with pCMV infection until early childhood. OBJECTIVES: To assess whether preterm infants with postnatal cytomegalovirus infection develop neurologic sequelae in early childhood. METHODS: Infants <32 weeks’ gestation were prospectively screened for cytomegalovirus (CMV) at term-equivalent age. Neurodevelopment was compared between CMV-positive and CMV-negative infants by using the Griffiths Mental Development Scales (GMDS) at 16 months’ corrected age (CA); the Bayley Scales of Infant and Toddler Development, Third Edition or the GMDS at 24 to 30 months’ CA; and the Wechsler Preschool and Primary Scale of Intelligence, Third Edition and Movement Assessment Battery for Children, Second Edition at 6 years of age. At 6 years old, hearing was assessed in CMV-positive children. RESULTS: Neurodevelopment was assessed in 356 infants at 16 months’ CA, of whom 49 (14%) were infected and 307 (86%) were noninfected. Infected infants performed significantly better on the GMDS locomotor scale. There were no differences at 24 to 30 months’ CA on the Bayley Scales of Infant and Toddler Development, Third Edition or GMDS. At 6 years of age, infected children scored lower on the Wechsler Preschool and Primary Scale of Intelligence, Third Edition, but mean scores were within normal range, reaching significance only in verbal IQ (96 [SD 17] vs 103 [SD 15] points; P = .046). Multiple regression indicated no impact of CMV status but significant influence of maternal education and ethnicity on verbal IQ. No significant differences in motor development were found and none of the infected children developed sensorineural hearing loss. CONCLUSIONS: In this cohort study, postnatal cytomegalovirus infection in preterm children did not have an adverse effect on neurodevelopment within the first 6 years of life.

Predictors of severity for postnatal cytomegalovirus infection in preterm infants and implications for treatment.

Postnatal cytomegalovirus (CMV) infection is common in neonates and is mostly acquired through infected breast milk from seropositive mothers. In this review, risk factors of postnatal CMV transmission and predictors of severity, preventive measures and treatment of symptomatic postnatal CMV infection in preterm infants are discussed. Several viral, transmission route and host factors have been associated with a higher risk of postnatal CMV transmission from mother to child. Severity predictors of symptomatic postnatal CMV infection may include extreme prematurity (gestational age <26 weeks), timing of postnatal infection as well as comorbidities. Further research in postnatally infected preterm infants at risk for severe symptoms is essential with respect to preventive measures involving the infected breast milk and antiviral treatment.

International opinions and national surveillance suggest insufficient consensus regarding the recognition and management practices of infants with congenital cytomegalovirus infections

This study evaluated the recognition and management practices with regard to congenital cytomegalovirus (cCMV) infections by a select group of experts and through a national surveillance study.

Congenital Cytomegalovirus Infection in the Absence of Maternal Cytomegalovirus-IgM Antibodies

Background: Congenital cytomegalovirus (cCMV) infections are the most prevalent intrauterine infections worldwide and are the result of maternal primary or non-primary infections. Early maternal primary infections are thought to carry the highest risk of fetal developmental abnormalities as seen by ultrasound; however, non-primary infections may prove equally detrimental. Methods/Results: This case series presents 5 cases with fetal abnormalities detected in the second and third trimester, in which cCMV infection was ruled out due to negative maternal CMV-IgM. Discussion: This series highlights the possible pitfalls in serology interpretation and fetal diagnosis necessary for appropriate parental counseling. Once fetal abnormalities have been confirmed and cCMV is suspected, maternal CMV serostatus and fetal infection should be determined. Maternal CMV serology may be ambiguous; therefore, caution should be exercised when interpreting the results.

PO-0557 Neuro-imaging In Infants With Congenital Cytomegalovirus Infection: Relation With Time Of Onset Of Infection During Pregnancy

Background Cytomegalovirus infection early in pregnancy results in major disabilities, including cerebral palsy and sensorineural hearing loss (SNHL). Cerebral abnormalities detected using cranial ultrasound (cUS) and magnetic resonance imaging (MRI) have been related to neurological sequelae. Objective To evaluate additional value of MRI and assess relationship between time of infection during pregnancy and outcome in infants with congenital cytomegalovirus (cCMV) infection. Patients and methods Demographic and clinical data were collected in infants with cCMV infection (1992–2013). Time of onset of infection during pregnancy, neuro-imaging results and outcome were reviewed. Cerebral abnormalities were categorised into none, mild (lenticulostriate vasculopathy (LSV), germinolytic cyst, high signal intensity T2 weighted images) and severe (migrational disorder, ventriculomegaly, cerebellar hypoplasia). Fisher exact test was used for statistical analysis. Results Thirty-five infants were eligible for analysis. cUS was performed in all and MRI in 19 infants. cUS was superior for diagnosing LSV (p < 0.01) and MRI for diagnosing migrational disorders (p < 0.01). In 17 infants time of onset of infection during pregnancy was ascertained. Eight of ten infants infected during first trimester had severe cerebral abnormalities and adverse sequelae, two had no or mild cerebral abnormalities and normal outcome. Two of three infants infected during second trimester had normal outcome and one developed SNHL. All four infants infected during third trimester had normal outcome. Conclusion Infants with first trimester cCMV infection are most at risk of severe cerebral abnormalities and neurological sequelae. MRI provides additional information for presence of migrational disorders, essential for early prediction of outcome.